A wide variety of warts are found on human skin and are caused by the human papilloma virus (HPV). For example, the following types of warts are found on human skin and are caused by the human papilloma virus (HPV): common warts (verruca vulgaris), plantar warts, palmar warts, planar warts (verruca plana), mosaic warts, and venereal warts (condyloma accuminatum). These skin growths are unsightly, irritating, and potentially oncogenic (carcinogenic), and their removal is desired.
Throughout the years a number of therapies have been developed for treating warts, and these therapies can be categorized in the following seven categories: (1) locally destructive chemicals; (2) surgically destructive methods; (3) blister-producing methods; (4) cellular inhibition; (5) altering the cutaneous environment; (6) immune stimulation; and (7) miscellaneous methods. See the article by Vance entitled "Verruca Vulgaris (Warts)", pages 743-745, in Conn's Current Therapy 1992, edited by Robert E. Rakel, M.D., W. B. Saunders Company, (1992).
Treatment methods using locally destructive chemicals include using the following chemicals: salicylic acid (in films, plasters, pads, and tapes); lactic acid; trichloracetic acid (TCA); bichloroacetic acid (BCA); nitric acid; and glacial acetic acid.
Surgically destructive methods include the following techniques: excision; electrocautery; electrodesiccation; curettage; blunt dissection; and laser vaporization or coagulation.
Blister-producing methods include the following techniques: liquid nitrogen cryotherapy; carbon dioxide cryotherapy; and cantharidin.
Cellular inhibition methods include use of the following agents: podophyllin and podophyllotoxin; 5-fluorouracil; bleomycin; colchicine; interferon local injections; and radiation.
Methods for altering the cutaneous environment include the following agents or techniques: retinoids; formalin; glutaraldehyde; aluminum chloride; and heat therapy.
Immune stimulation methods of treatment include the following: dinitrochlorobenzene (DNCB); interferon systemic injections; and vaccination, autologous or intralesional.
Miscellaneous methods include: hypnosis; and tape occlusion. On page 745 of the Vance article, there is a statement that hypnosis and tape occlusion probably have a placebo effect providing an about 20% cure.
Currently, there are a number of over-the-counter products on the market that are used for treating warts. One such product is Pedia Patch (TM) of Tsumura International, Inc., Shakopee, Minn. 55379. This product contains a quantity of salicylic acid in a sticky base. The salicylic acid/sticky base is retained and carried by a piece of adhesive tape. In use, the salicylic acid/sticky base is applied to the wart, and free ends of the adhesive tape are applied to peripheral skin areas to keep the treating agent in place on the skin. This product employs two of the above-mentioned seven wart treatment methods simultaneously, namely: (1) a locally destructive chemical (salicylic acid); and (7) tape occlusion.
A second over-the-counter wart treatment product is Duo Plant (R) a plantar wart removal system of Schering Plough, Healthcare Products, Inc., Memphis, Tenn. 38151. This product is a gel that includes alcohol 57.6% w/w, ether 16.42% w/w, ethyl lactate, hydroxypropyl cellulose, and polybutene in flexible collodion. The gel is applied directly to the wart, and the solvents evaporate leaving a film with treating agent.
A third over-the-counter wart treatment product is Dr. Scholls Clear Away Plantar Wart Remover System (TM) of Schering Plough Healthcare Products, Inc., Memphis, Tenn. This product includes adhesive-tape-containing discs which contain salicylic acid (40%) in a rubber-based vehicle. The salicylic acid/rubber base is retained and carried by the piece of adhesive tape. In use, the salicylic acid/rubber base is applied to the wart, and free ends of the adhesive tape are applied to adjacent skin areas to keep the treating agent in place on the skin. This product employs two of the above-mentioned seven wart treatment methods simultaneously, namely: (1) a locally destructive chemical (salicylic acid); and (7) tape occlusion.
A fourth over-the-counter wart treatment product is Compound W (TM) of Whitehall Laboratories, Inc., New York, N.Y. 10017. The active ingredient in the product is salicylic acid (17% w/w). Inactive ingredients in the product include: acetone; collodion; alcohol (2.2% w/w); camphor; castor oil; ether (63.5%); menthol; and Polysorbate 80. In use, this product is applied as a liquid coating to a wart. When the solvents evaporate, the wart is covered by a flexible film which contains the active ingredient.
Fifth and sixth over-the-counter wart treatment products are Transplantar (TM) and Transversol (TM), respectively, made by Bradley Pharmaceutical Co., 383 Route 46 West, Fairfield, N.J. 07004. Each of these products employs salicylic acid in a gum base. A piece of adhesive tape retains and carries the salicylic acid/gum base composition. In use, the salicylic acid/gum base composition is placed over the wart, and the adhesive tape is applied to adjacent skin to keep the device in position. This product employs two of the above-mentioned seven wart treatment methods simultaneously, namely: (1) a locally destructive chemical (salicylic acid); and (7) tape occlusion.
Another wart treatment product is Occlusal-HP (TM), by Gen Derm Corporation, Lincolnshire, Ill. 60069. It is noted that Occlusal HP contains 17% salicylic acid in a polyacrylic vehicle containing ethyl acetate, isopropyl alcohol, butyl acetate, polyvinyl butyral, dibutyl phthalate, acrylates copolymer, and nitrocellulose. The pharmacologic activity of Occlusal-HP is generally attributed to the keratolytic action of salicylic acid which results in mechanical removal of epidermal cells infected with wart viruses.
Another wart treatment product is a plaster called Sal-Acid Plaster (TM) by Pedinol Pharmacal, Inc., 30 Banfi Plaza, Farmingdale, N.Y. 11735. This product contains 40% salicylic acid.
Yet another wart treatment product is disclosed in the 1990 edition of the Physicians Desk Reference (PDR), published by Medical Economics Data Production Company, Montvale, N.J. This wart treatment product is Viranol (TM) gel made by American Dermal Corp., Bedminster Industrial Park, P.O. Box 900, Plumsteadville, Pa. 18949. Viranol gel has 12% salicylic acid as its active ingredient.
Aside from the treatments mentioned above which have attained the status of generally accepted methods and techniques in medical practice for treating warts, there are publications in the literature which disclose still other methods and techniques for treating warts. Of special relevance with respect to the present patent are publications which disclose anthralin or its analogs or derivatives in the treatment of warts.
Anthralin is also known as dithranol, and its chemical name is 1,8-dihydroxy-9(10H)-anthracenone. An alternate chemical name for anthralin is 1,8-dihydroxyanthrone. Still another accepted chemical name for anthralin is 1,8-dihydroxy,9-anthrone. Commercial preparations containing anthralin include Anthra-Derm, Antraderm, Batidrol, Cignolin, Cigthranol, Drithocreme, Psoradrate, and Psoriacide. The triacetate is known as 1,8,9-anthracenetriol triacetate and, alternatively, as 1,8,9-triacetoxyanthracene, which is known commercially as Exolan. See The Merck Index, Tenth Edition, (1983) for the entry "Anthralin".
In an article by Flindt-Hansen et al entitled "Wart Treatment With Anthralin", in Acta. Derm. Venereol. (Stockh.) 64: 177-180, 1984, there is a disclosure that 27 patients were treated with Anthraderm (2% anthralin and 0.5% salicylic acid in a wax preparation enclosed in a lipstick-like container). More specifically, the treatment involved application of the Anthraderm twice a day by the patients. Every 2 weeks gentle cutting and scraping of the warts were performed in a clinic. Undergoing this treatment of topical application of Anthraderm and periodic cutting and scraping, 15 (56%) of the 27 patients were cured; that is, no wart tissue was visible. There is a teaching that in psoriasis, the effect of anthralin is thought to consist in a reduction of the cell turn over caused by an inhibition of the cell metabolism. These pharmacological effects in the cell metabolism might be beneficial in the treatment of the benign tumour produced by replicating wart virus. There is no disclosure that any tape occlusion was used.
In an article by Hjorth et al entitled "Anthralin Stick (Anthraderm) in the Treatment of Mosaic Warts", in Acta. Derm. Venereol. (Stockh.) 66: 181-182, 1986, there is a disclosure that anthralin in a wax-based stick (2% anthralin stick) that was used for 2 months was effective against common warts. More specifically, there were 30 patients treated. After a mean of 7 months of treatment (range, 3 to 10 months), warts in 17 patients were cleared, and warts in 7 patients persisted. The remaining 6 patients dropped out. The treatment involved daily application of 2% anthralin stick supplemented by weekly paring (cutting or shaving) of the wart. By having 17 patients out of 30 patients cleared of warts, the percentage of patients cleared of warts is 57%. There is no disclosure that any tape occlusion was used.
In an article by Mare et al entitled "Dithranol in the Treatment of Inflammatory Linear Verrucous Epidermal Nevus" in Acta Derm Venereol (Stockh), Vol. 69 (Short Reports), pages 77-80, (1989), there is a disclosure that dithranol (also known as anthralin) was used to treat a patient with the short contact anthralin therapy (SCAT) method to treat the psoriasis condition known as inflammatory linear verrucous epidermal nevus (ILVEN). Over an 8 week period, the concentration of the anthralin was increased in the following increments in the short contact anthralin therapy (SCAT) method: 0.5%, 1%, 2%, 3%, 4%, and 5%. There is no disclosure that the anthralin was used in treating common warts. There is no disclosure that any tape occlusion was used.
By and large, anthralin is used primarily in the treatment of psoriasis. Psoriasis is a condition of the skin in which skin cells mature abnormally rapidly resulting in increased cellular turnover and rapid growth of the skin. There is no involvement of the human papilloma virus (HPV) in psoriasis. Aside from anthralin, other conventional treatments for psoriasis include topical corticosteroids, tar, UV-B radiation, psoralens and UV-A radiation, and bland emollients.
More specifically with respect to the treatment of psoriasis, the following U.S. patents discloses compositions containing anthralin or its derivatives or analogs for treating psoriasis: U.S. Pat. Nos. 4,465,688; 4,495,203; 4,504,494; 4,696,941; and 4,866,095. More specifically, in U.S. Pat. No. 4,465,688, from column 13, line 49 to column 14, line 2, a composition is disclosed which contains 9,10-dihydro-1,8,9-trihydroxy-9,10-anthracene-alpha,beta-endo-N-ethyl succinimide (a compound related to anthralin) approximately 1.47% by weight; salicylic acid, approximately 0.68% by weight; and petroleum jelly, approximately 97.85% by weight. The composition is prepared in the form of a suspension that is applied once a day for three weeks. Excellent results are obtained on the psoriasis areas very similar to those obtained with anthralin but with no primary irritation and without staining of the skin. In this patent there is a nominal disclosure that warts can also be treated with the 9,10-dihydro-1,8,9-trihydroxy-9,10-anthracene-alpha,beta-endo-N-ethyl succinimide, but no specific protocol for treating warts is disclosed. In this respect, there is no disclosure that any tape occlusion is used for treating warts with the 9,10-dihydro-1,8,9-trihydroxy-9,10-anthracene-alpha,beta-endo-N-ethyl succinimide. U.S. Pat. No. 4,866,095 has disclosures similar to U.S. Pat. No. 4,465,688.
U.S. Pat. No. 4,504,494 discloses that anthralin compositions are used in the treatments of psoriasis and warts. In this patent, Examples IV, VII, VIII, XIII, and XIV disclose compositions which contain anthralin and an aromatic ester vehicle. Some of the examples also contain a solid material such as silica. The patent gives special emphasis to the treatment of psoriasis. There is no specific disclosure on the treatment of warts with anthralin. Also, there is no disclosure that any tape occlusion is used. U.S. Pat. No. 4,495,203 has disclosures similar to U.S. Pat. No. 4,504,494.
U.S. Pat. No. 4,696,941 discloses compounds related to anthralin that are used in the treatment of psoriasis, acne, warts, and rheumatism. Treatment of psoriasis, acne, and warts is by topical treatment. Treatment of rheumatism is by injection. Examples 9-18 disclose topically administrable compositions. There is no specific example of treatment of warts. Also, there is no disclosure that any tape occlusion is used.
Additional publications relating to the use of anthralin to treat psoriasis are discussed below.
In an article by Gottlieb et al entitled "Anthralin Decreases Keratinocyte TGF-alpha Expression and EGF-Receptor Binding in Vitro", in The Journal of Investigative Dermatology, Vol. 98, No. 5, May 1992, pages 680-685, there is a disclosure that anthralin is an effective topical treatment for active psoriasis. It is suggested that pharmacologically relevant concentrations of anthralin have the ability to strongly inhibit keratinocyte proliferation in vitro, possibly by affecting early steps in mitogenic signalling pathways. Anthralin diminishes ligand binding to the epidermal growth factor (EGF) receptor via a reduction in binding affinity. There are teachings that anthralin treatment has been reported to inhibit granulocyte function, inhibit the lipoxygenase pathways, inhibit DNA replication and repair, inhibit mitochondrial respiration, and decrease calmodulin activity in vitro. In vivo, anthralin decreases plasminogen activator levels in plaques, inhibits mitochondrial ATP synthesis, and normalizes keratin expression. There is no disclosure of any treatment methods that employ anthralin that make use of an irritant response generated by anthralin. In this article, there is no disclosure of the use of anthralin in treating warts. Moreover, there is no disclosure that any occlusion device was used.
In an article by Ashton et al entitled "Anthralin: Historical and Current Perspectives" in the Journal of the American Academy of Dermatology, Volume 9, Number 2, August 1983, pages 173-191, there is an extensive review of the uses of anthralin therapy. The only medical condition discussed in the entire article that is treated with anthralin is psoriasis. There is no mention whatsoever of the use of anthralin to treat warts. On pages 187-188, there are recommendations for the use of anthralin in treating psoriasis. Since anthralin has the immediate side effects of skin irritation and staining, its use should be closely monitored. In essence, the irritant effects of anthralin are to be avoided in the treatment of psoriasis. Anthralin is administered in the form of the commercially available Drithocreme (TM).
In the Physicians' Desk Reference, 1993, under a listing for American Dermal Corporation, Plumsteadville, Pa. 18949, Drithocreme (TM) is disclosed to be comprised of anthralin (approximately 0.1%, 0.25%, 0.5%, or 1%) in a base of white petrolatum, sodium lauryl sulfate, cetostearyl alcohol, ascorbic acid, salicylic acid, chlorocresol, and purified water.
In the Ashton et al article, In Table II on page 187, there are suggested guidelines for home use of anthralin cream (Drithocreme(TM)) or ointment (Anthra-Derm(TM)) in the treatment of psoriasis. The guidelines suggest that anthralin should start a 0.1% and increase to 0.25%, 0.5%, and 1%. The treatment should continue for 1 to 2 weeks with this step-wise increase in the strength of the anthralin. The stepwise increase in the concentration of the anthralin used is to avoid skin irritation; that is, to avoid an irritant response. Moreover, on page 188, there is a suggestion that "short contact therapy" may be a practical outpatient therapy for the future.
It is noted that Drithocreme (TM) described in the Physicians' Desk Reference listing for American Dermal Corporation, Plumsteadville, Pa. 18949 is currently a product of Dermik Laboratories, Inc., Collegeville, Pa. Drithocreme (TM) is available in four concentrations (approximately 0.1%, 0.25%, 0.5%, and 1%[HP]) for the treatment of psoriasis. In literature published by Dermik Laboratories for using Drithocreme (TM), it is recommended that the 0.1% strength anthralin formulation of Drithocreme (TM) be used for at least one week to assess each patient's individual tolerance to anthralin.
In an article by Lowe et al entitled "Anthralin for psoriasis: Short-contact anthralin therapy compared with topical steroid and conventional anthralin", in Journal of the American Academy of Dermatology, Vol. 10, No. 1, pages 69-72, January 1984, there is a disclosure that conventional overnight (approximately 8 hours) anthralin therapy for psoriasis uses anthralin in a range of 0.1%-0.5% anthralin. On page 70 there is a statement that no higher concentration than 0.5% was used in conventional anthralin therapy for psoriasis, as higher concentrations in petrolatum would be irritating if left on overnight. It is clear that in the treatment of psoriasis, the irritant effects of anthralin are to be avoided. On the other hand, higher anthralin concentrations, in the range of 0.5%-3%, are left on for 10 minutes and then washed off with soap and hot water. With this short contact anthralin therapy, the initial concentration of anthralin was 0.5%, and this was increased to 1% and 3% at 3-day intervals. A key objective of the short contact anthralin therapy is to avoid an irritant response to anthralin.
A brochure published by Dermik Laboratories, Inc. entitled "Anthralin Therapy Simplified", that accompanies the Drithocreme (TM) product, includes text of a letter written by Nicholas J. Lowe, M.D., the same Dr. Lowe who coauthored the above-mentioned article. The Lowe letter discloses that Drithocreme (TM) can also be used for short contact anthralin therapy (SCAT) for treating psoriasis without causing skin irritation. The SCAT method of treating psoriasis is employed with a key intended purpose of avoiding an irritant/immunologic response to anthralin. The recommended dosage and contact time for Drithocreme (TM) is Drithocreme (TM) containing 1% anthralin for 10 minutes. However, under certain circumstances, short contact anthralin therapy can be employed up to 60 minutes. There is no disclosure of the use of any concentration of Drithocreme (TM) for treating warts. In addition, there is no disclosure that Drithocreme (TM) any tape occlusion was used.
In an article by De Groot et al entitled "Contact allergy to dithranol" in Contact Dermatitis, Vol. 7, pages 5-8, 1981, there is a disclosure that a patient having common warts on the hands was treated with collodion containing dithranol 3%, salicylic acid 25%, and acetone 10%. After two applications, the patient had stopped the treatment because she experienced itching and noticed small blisters on the her hands. Examination of the patient showed a systemic response; that is, there were papulovesicular eczematous lesions on both arms, legs, and abdomen. The hands showed an oozing vesicular dermatitis, the warts being swollen. The eczematous reaction subsided with topical steroid medication in a couple of days. After running a series of patch tests, it was determined that the patient was allergic to dithranol. Three weeks after two applications of the collodion containing the dithranol 3%, salicylic acid 25%, and acetone 10%, all warts had completely cleared. The authors theorized that the curing of the warts in the patient was probable attributable to the contact allergic dermatitis induced by dithranol. This patient was a relatively rare person who had a contact dermatitis to dithranol. There is no suggestion in the article that most patients, not having a systemic allergic response to dithranol, are to be treated with dithranol to elicit an irritant response in the treatment of warts. In this article, there is also a disclosure that patients suffering from the condition known as alopecia areata were simultaneously treated with dithranol and 2,4-dinitrochlorobenzene (DNCB) wherein the DNCB is a known immuno-stimulating agent. As a result, these patients had a contact allergy to dithranol. There is no disclosure that tape occlusion was employed in any of the treatment methods.
In an article by Kanerva entitled "Electron microscopic observations of dyskeratosis, apoptosis, colloid bodies and fibrillar degeneration after skin irritation with dithranol", in J. Cutan. Pathol., Vol. 17, pages 37-44, 1990, there is a disclosure that healthy skin on the backs of volunteers was treated with dithranol using the epicutaneous Finn chamber occlusion technique. The dithranol concentrations used were 0.2% dithranol in petrolatum and 0.1% dithranol in petrolatum. The results were the observations, under the electron microscope, of dyskeratosis, apoptosis, colloid bodies and fibrillar degeneration after skin irritation of the healthy skin with dithranol. There is a statement on page 37 that cell-mediated immunity is believed to play an important role in regression (not treatment) of plane warts. On page 43, there is a statement that immunocompetent lymphocytes are seen under the electron microscope to be apposed to Langerhans cells (LC) after dithranol irritation. In the article, dithranol is referred to as an anti-psoriatic drug, and there is no mention of the treatment of warts in this article. Also, there is no mention of the use of tape occlusion.
As stated above, warts are caused by the human papilloma virus (HPV). There are findings reported in the literature that human papilloma virus may be implicated in certain forms of cancer See Franceschi et al, "Genital warts and cervical neoplasia: An epidemiological study", Br. J. Cancer, Vol. 48, pages 621-628, (1983) and Crum et al, "Human papillomavirus Type 16 and Early Cervical Neoplasia", The New England Journal of Medicine, Vol. 310, No. 14, pages 880-883, (Apr. 5, 1984). In view of the link between the human papilloma virus and cancer, the prompt and effective treatment and destruction of warts is strongly indicated.
Upon reviewing the prior art cited above, certain conclusions can be made about the prior art as a whole. First, none of the prior art discloses the use of an anthralin with tape occlusion to treat warts. Second, the prior art treatments of warts which do involve tape occlusion include only solid materials such as solid salicylic acid. Third, tape occlusion for treating warts is not disclosed as being used with a liquid or pasty material.
A fourth conclusion that can be made about the prior art is that of the seven techniques for treating warts discussed above (that is: (1) locally destructive chemicals; (2) surgically destructive methods; (3) blister-producing methods; (4) cellular inhibition; (5) altering the cutaneous environment; (6) immune stimulation; and (7) miscellaneous methods), tape occlusion (in technique No. 7) is used in conjunction only with technique No. 1 which involves the locally destructive chemical salicylic acid. Tape occlusion is not used in conjunction with technique Nos. 2-6.
A fifth conclusion that can be made about the prior art is that tape occlusion by itself probably has a placebo effect providing an about a 20% cure.
A sixth conclusion that can be made about the prior art is that the treatment of warts with anthralin without concomitant tape occlusion (as described by Flindt-Hansen et al and Hjorth et al) has resulted in a wart clearing rate no greater than 57%.
A seventh conclusion that can be made about the prior art is that the mode of operation of anthralin in the treatment of warts is thought to consist of a reduction of the replication of the wart virus caused by an inhibition of the cell metabolism.
An eighth conclusion that can be made about the prior art is that immune stimulation methods of wart treatment do not include anthralin as an immune stimulating agent.
A ninth conclusion that can be made about the prior art is that there is no disclosure of any treatment methods employing tape occlusion that make use of an immune response generated by an active ingredient. As a corollary conclusion, there is no disclosure of any wart treatment methods employing tape occlusion that make use of an immune response generated by anthralin.
A tenth conclusion that can be made about the prior art is that anthralin is employed in the treatment of psoriasis in a manner clearly designed to avoid an undesired immunologic/irritant response to anthralin.
An eleventh conclusion that can be made about the prior art is that when salicylic acid is used with tape or film occlusion for treating warts, the range of salicylic acid is in a range of 17% to 40%. In this respect, it is recalled that in Compound W (TM) of Whitehall Laboratories, Inc., New York, N.Y. 10017, the active ingredient in the product is salicylic acid at 17% w/w. It is also recalled that in the article by De Groot et al entitled "Contact allergy to dithranol" discussed above, there is a disclosure that a patient having common warts on the hands was treated with collodion containing dithranol 3%, salicylic acid 25%, and acetone 10%. It is further recalled that in Dr. Scholls Clear Away Plantar Wart Remover System of Schering Plough Healthcare Products, Inc., Memphis, Tenn., the product includes adhesive-tape-containing discs which contain salicylic acid (40%) in a rubber-based vehicle.
A twelfth conclusion that can be made about the prior art is that when salicylic acid is used to stabilize (acidify) an anthralin, salicylic acid is present in an amount of less than 2.0% by weight. In this respect, it is recalled that in U.S. Pat. No. 4,465,688, from column 13, line 49 to column 14, line 2, a composition is disclosed which contains 9,10-dihydro-1,8,9-trihydroxy-9,10-anthracene-alpha,beta-endo-N-ethyl succinimide (a compound related to anthralin) approximately 1.47% by weight; salicylic acid, approximately 0.68% by weight; and petroleum jelly, approximately 97.85% by weight. It is also recalled that an anthralin ointment employs a pharmaceutical carrier described in the British Pharmacopoeia as Lassar's paste. This carrier includes 240 g. of zinc oxide finely sifted, 20 g. of salicylic acid finely sifted, 240 g. of starch finely sifted, and 500 g. of white soft paraffin. Anthralin ointments containing the Lassar's paste can include anthralin in concentrations ranging from 0.5% to 5.0%. Thus, the percentage of salicylic acid in a Lassar's paste based ointment is less than 2.0% by weight.
A thirteenth conclusion that can be made from the prior art is that a therapeutic amount of salicylic acid for treating warts by tape or film occlusion is equal to or greater than 17% salicylic acid by weight.
A fourteenth conclusion that can be made about the prior art, which is a corollary of the thirteenth conclusion, is that the presence of salicylic acid in a composition for treating warts by tape or film occlusion in an amount less than 17% by weight of the composition is a less than therapeutic amount of salicylic acid for treating the warts.
In forming a fifteenth conclusion, it is recalled that the lowest percentage of salicylic acid in a wart treating composition that is discussed hereinabove is 12% salicylic acid in Viranol gel. From the percentage of salicylic acid in Viranol and from the percentages of salicylic acid in other wart-treating products, it may be concluded that the lowest effective percentage of salicylic acid in a wart treating composition is 12% salicylic acid. It is noted, however, that Vironal gel is not used with tape occlusion.
Considering a prudent 3% margin of error with respect to the 17% therapeutic amount of salicylic acid for tape occlusion for treating warts, it is further concluded, as a sixteenth conclusion, that an amount of less than 14% by weight of salicylic acid for tape occlusion for treating warts is less than a therapeutic amount of salicylic acid for tape occlusion.
Furthermore, considering a prudent 3% margin of error with respect to the 12% therapeutic amount of salicylic acid in Vironal gel for treating warts topically, it is further concluded, in a seventeenth conclusion, that an amount of less than 9% by weight of salicylic acid for treating warts topically (without tape occlusion) is less than a therapeutic amount of salicylic acid for topical treatment of warts.